An in vitro approach for studying the organ, species, strain and individual variations in the activation of chemical carcinogens has been developed. Rat, mouse, hamster, bovine, and canine species have been used extensively with liver and bladder being the primary organs studied. Both intact cells and cell homogenates have been used for activation. To assess biological activity, the multiple genetic endpoints of toxicity, SCE and mutation induction in V79 cells and/or reversion of Salmonella typhimurium are used. Species, strain and organ differences have been observed for chemicals such as nitrosamines, aromatic amines, hydrocarbons, and carbamate derivatives. In general, the relative mutagenic or cytogenetic activity correlates with the in vivo carcinogenic activity.